DESCRIPTION (Investigator's abstract): Environmental factors have either an etiologic or modulatory role in the phenotypic presentation of tics in Tourette syndrome (TS). It has been shown that a subset of children with TS, designated TS-PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection), develop tic symptoms after a Group A beta-hemolytic streptococcal (GABHS) infection. The pathogenesis of tics in this subset of TS has been postulated to involve anti-neuronal antibodies (ANAb), similar to the pathophysiology in Sydenham's chorea. In support of an immune-related hypothesis for TS, our preliminary studies showed that a) serum antibodies to human putamen, but not to caudate or globus pallidus, are significantly increased in children with TS and b) after intrastriatal injection of purified serum IgG from TS patients, rodents developed dyskinesias associated with antibody binding to striatal neurons. The specific aims of this proposal are, in a cohort study, to examine the relative contribution of ANAb levels and streptococcal infections to exacerbations of tics in 50 children with TS-like PANDAS, 50 with TS-nonPANDAS, and 50 Controls (ages 6-13 years). At baseline, after an exacerbation of tics, and 6 weeks thereafter, serum ANAb titers against caudate, putamen and globus pallidus will be measured by ELISA (Aim 1), and Western blot analysis (Aim 2). Aim 3 will test whether speculated elevated ANAb titers and specific Western blot bands in TS-PANDAS will be reduced by preabsorption of serum with streptococcal cell wall proteins extracted with group C phage lysin and with streptococcal M-proteins (wild and recombinant). ANAb titers/specific bands, measured at baseline, after an exacerbation of tics, and 6 weeks thereafter, will be compared to changes in tic severity, obsessive-compulsive behaviors, and GABHS markers (ASO and anti-DNAse B) (Aim 4). Aim 5 will evaluate the presence of ANAb (ELISA and Western blot) in serum from children with Sydenham's chorea. Aim 6 will assess whether the presence of the B lymphocyte antigen D8/17 is a genetic susceptibility "fingerprint" specific for the TS-PANDAS group. The long-term objective is the documentation of specific immune-mediated mechanism for TS.